The immune system and the human body: we’re not alone

It’s something you need, and it is given to you at birth. It’s something you eat, but you don’t think about eating. It can be both good and bad, but it’s essential. What is this mystery element? It is bacteria!

You are exposed to bacteria as early as birth, whether it be through physical contact, ingestion, or inhalation. Newborn babies, excluding those that are born through Caesarean section, are exposed to bacteria through the mother’s vaginal tract, and this is actually the first contact. Eventually, your body will contain 10 times the number of bacterial cells nestled within your digestive tract as the number of cells in your entire body. That is about 100 trillion cells of bacteria in your body! How, then, do you not become overwhelmed by this growth of bacteria? The secret is in the immune system.

The bacteria in your digestive tract, collectively termed gut flora, is normally composed of up to 1000 different species. These organisms can form one of several relationships with the human body. Some bacteria may consume large amounts of nutrients from the human body and make you vulnerable to disease, which is parasitism. In contrast, some bacteria take nutrients, but do not render any ill effects, which is commensalism. The third relationship, termed mutualism, is when bacteria are essential at aiding the host, such as developing the immune system, while necessarily requiring the nutrients of its host. All three relationships have been important topics to the scientific community, and by studying gut flora in different model organisms, scientists can learn more about the roles these bacteria play, particularly in shaping the immune system.

Immune cells, such as dendritic cells and macrophages, regularly engulf and digest organisms to breakdown into molecules. The molecules are then presented by the immune cell to alert the immune system to possible harmful bacteria or other pathogens.

A macrophage (center) extending its cell body to the left and right to engulf two particles.

The Toll-like receptor 2 (TLR 2) is a protein receptor utilized by immune cells to recognize some of these gut microbes before these molecules are presented by the immune cell. By having receptors, such as the TLR 2, the immune system can survey its surroundings to ensure that no critical mass of harmful organisms develop.

Researchers at the University of Sāo Paulo, Brazil found that gut flora are essential to regulating insulin resistance. This research involved knocking-out (KO) the TLR 2 receptor in mice, essentially removing it from the immune system, to make the host vulnerable to unchecked levels of bacteria. These KO mice exposed to bacteria, compared to KO mouse grown in germ-free environments, developed a metabolic syndrome characterized by obesity and insulin resistance. Essentially, the host immune response must develop strong checkpoints to guard against gut flora in order to maintain healthy conditions. This is why it’s not always best to keep your kids away from “dirty” pets, insects, or surfaces that may actually aid in slowly building the immune system. In fact, this idea has fueled the hygiene hypothesis: some scientists believe that allergies can be due to a lack of early childhood exposure to organisms. The early childhood development of the immune system can help prime immune responses for future exposures!

One important quality of gut flora to host health is its composition, in terms of percentage and types. When this composition is altered, dysbiosis can lead to diseases such as inflammatory bowel disease or chronic fatigue syndrome. In a related study to metabolic syndrome, scientists analyzed the gut microbiota of Old Order Amish in order to understand the gut composition for this disease. Researchers found that there were 22 different species of bacteria that were either highly or lowly disproportionate to other bacterial species found in these patients with metabolic syndrome compared to healthy patients. Dysbiosis has even been a strong indicator for those with autism.

A study found that a group of 20 autistic children had significantly lower levels of the genera Prevotella, Coprococcus, and Veillonellaceae, which are all important bacteria that aid in carbohydrate digestion and/or fermentation. The build-up of these usually digestible carbohydrates or the lack of fermentation may be a relevant issue in the development of autism.

However, dysbiosis has a rather interesting treatment called fecal bacteriotherapy, and it has received great attention because of its success. This unique therapy, referenced as ‘RePooPulating’ in this scientific study, involves rectifying the dysbiosis in patients that causes inflammatory bowel disease. Recurrent bacterial infections of Clostridium difficile are the main cause of inflammatory bowel disease.

Fecal matter at 10,000x magnification.

The process involves transferring some of the gut flora from a healthy patient with normal bacterial composition into someone that has dysbiosis. Interestingly enough, fecal matter from a normal patient can be transplanted into infected patients via the rectum. It’s ironic that something disgusting can be so healthy for you! But, that’s not to say that you should save some of your poop for a rainy day. For more insight into fecal bacteriotherapy, visit this PLOS blog by Beth Skwarecki.

It’s quite amazing how gut flora play an integral role in the human body and the impact it has on the immune system. The relationship must have evolved through many ancestrally-related species, as humans are far from the first to have an immune system, to account for the development of the complex relationship to the diverse collection of bacteria. The intricate, yet fragile, relationship even extends to neurological diseases such as autism. So, the next time you decide to get something to eat, realize it’s more than just calories.

Who wants chocolate-dipped ice cream?

Marvin is a PhD candidate at Stanford University in Immunology. He was an editor-in-chief at the Caltech Undergraduate Research Journal. See it at curj.caltech.edu. Follow on twitter @Marvzipan. gee.marvin@gmail.com

About Marvin Gee

Marvin Gee is a PhD candidate at Stanford University in the field of Immunology. Marvin was a past editor-in-chief for the Caltech Undergraduate Research Journal at curj.caltech.edu.

Thanks for this well-researched article Marvin. In 20 years time I think we will see a very different approach to management of autoimmune illnesses, one that will involve gut flora and preserving the integrity of the gut wall. Much better to protect the immune system nature gave us than to medicate it when it breaks down.

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